The first step to adding T3 to our thyroid hormone replacement regimen following total thyroidectomy (TT) is understanding what T3 is and how it works.
The two thyroid hormones are thyroxine (T4) and triiodothyronine (T3). A healthy thyroid produces mostly T4 and smaller amounts of T3. This production is controlled by a “negative feedback loop” called the hypothalamic–pituitary–thyroid axis (HPT).
T4 produced by the thyroid is called thyroxine. The synthetic version of T4 is levothyroxine, the form most often prescribed after thyroid surgery. T4 is a prohormone — it has minimal effect until it is converted to T3 and other metabolites by a process called deiodination which removes an iodine atom.
Biologically Active T3
T3 produced by the thyroid or converted from T4 is called triiodothyronine. The synthetic version is called liothyronine. T3 is the biologically active hormone and affects almost every physiological process in the body, including growth and development, metabolism, body temperature, and heart rate, and is used by our cells for energy production.
Several other T4 derived metabolites are being studied to determine what influences they may have.
Combination Therapy is thyroid hormone replacement (THR) therapy which combines both T4 and T3 to more closely mimic normal thyroid function. Because T3 has a short half life, the dose is usually divided into two or three doses during the day. It may use synthetic or “natural” (DTE) forms of thyroid hormone.
Desiccated Thyroid Extract (DTE) is thyroid hormone extracted primarily from freeze dried porcine (pig) thyroids, also called Natural Desiccated Thyroid (NDT). It includes both T4 and T3 in standardized amounts as a prescription medicine. DTE is considered by some to contain metabolites and calcitonin not provided by synthetic hormones.
Wired and Tired
Following TT, a TSH suppression goal is usually determined based on pathology and other risk of recurrence factors. Using T4 alone at high doses to reach the TSH goal can sometimes cause symptoms of over medication — anxiety, palpitations, unintended weight loss — while not relieving symptoms of inadequate T3 — fatigue, “brain fog” and poor focus, dry skin, brittle hair and nails. A phrase coined by one thyroid cancer advocate is “Wired and Tired” and this constellation of both “hyper” and “hypo” thyroid symptoms is a frequent complaint on thyroid cancer message boards. Often, the T4 dose can be lowered and T3 added to achieve the suppression goal without causing the symptoms related to over medication with T4.
Deciding to Include T3
Adding T3 is a choice made with your physician based on response to therapy including clinical evaluation of symptoms and laboratory (chemical) results. When taking this step, some things need to be kept in mind.
T4 has a fairly long active half life — the time it takes for 50% of substance to leave your body — averaging 6-7 days. This means it can take a few to seven days or longer to feel changes or for lab results to change.
T3, on the other hand, has a rapid onset and peak level— about four to six hours. Half life is described by different sources as <1-2 days, 2-1/2 days or 2-3 days but there seems to be agreement that a steady state is achieved in 2-3 days. It also has a rapid cut off of action though some heart rate effect may persist for up to 72 hours.
Four by Four
Based on these pharmacokinetics, the reported experiences of myself and others, and extensive research I’ve considered a “Four by Four” approach to starting T3. That is Four Hours between doses and Four Days between changes.
A general rule is to start T3 slow and low. First you need to determine with your physician if you need to lower your T4 dose before starting T3, based on laboratory results for Free T4 and any symptoms you’re experiencing. Then you need to determine your target T3 dose based on laboratory results for Free T3 and symptoms. You should also agree on a maximum target or goal — 15 or 20 mcg (using 5 mcg tablets) is not unreasonable when you are following a structured plan to reach that goal. You may never require that maximum dose but having the flexibility to slowly adjust and titrate ensures success.
If you need to lower your T4, do that before beginning T3. Wait until any over medicated symptoms have lessened — possibly skipping a day to speed this up if your doctor agrees. Some people find that starting T3 is easier if their levothyroxine is taken at night
The first few days, just take a portion of your target T3 dose in the morning. This may be in the range of 2.5 or 5.0 mcg. You can take it the same time as your T4 or later in the morning — whatever works for you. At 2.5 mcg you might not notice any change but this will give you a chance to see how sensitive you are to the T3 and how it feels later in the day when the morning dose wears off.
After a few days (remember Four by Four) add another small dose in the afternoon, about four to six hours following the morning dose. So now you might be taking 2.5 mcg or 5.0 mcg in the morning and another 2.5 or 5.0 mcg in the afternoon. In another three or four days you should be noticing some, even if very small, improvement. If you’ve been using something like the Symptom Checklist, it’s easier for you to notice and keep track of small changes plus having a record to show your doctor.
If you feel you need another increase after four days, either add a small amount to your morning dose or add in a third small dose. Many of us tolerate increases better in the morning but what works best for you will depend on your schedule and lifestyle. Especially when starting out, increases in the afternoon may keep you from sleeping well. It may take some time to find your own personal rhythm.
If you have reached your target dose OR if you have reached a dose where you feel you’ve made a good improvement, you can retest in four to six weeks. This will give time for both Free T3 and Free T4 to be at a steady state, though your TSH may lag in either direction.
Make sure when you retest that
- You’ve stopped anything containing biotin for at least 72 hours,
- you have your blood drawn in the morning before you take any meds or
- you schedule the lab at least six to eight hours following your last dose.
One way to do this is to set an alarm on lab day and take your meds early so you can have at least a six hour or longer window. It’s also helpful to try to test at the same time of day each time and use the same laboratory. If you must use another lab which uses different reference ranges, compare results using Percent in Range.
If your doctor agrees with setting a maximum target T3 dose of 10 or 15 mcg, don’t feel you have to get to that immediately. In fact, you might find you don’t need that much at all. Setting a maximum target assures your provider that you can titrate up the dose safely with a plan and a goal in mind.
Some people do jump right into their full T3 dose or take it once a day instead of dividing and do just fine. Most of us have found we get much better results dividing our doses and making small changes slowly. We are all individual.
Use the Symptom Tracker to monitor your heart rate, blood pressure, improvements in daily activities. If you have any symptoms like palpitations, back up a step, then decide if you want to stay at that level or retry with a smaller increase. Body changes such as dry skin or hair loss may take longer to become obvious.
Don’t be discouraged and remember our thyroid hormone replacement therapy is for life, so it’s worth taking the time we need to learn, experiment and find what works best for us.
T4 – thyroxine, levothyroxine, Synthroid
T3 – triiodothyronine. liothyronine, Cytomel
DTE – desiccated thyroid, NDT, Armour
Biotin – interferes with thyroid tests, giving false levels
Shahid MA, Ashraf MA, Sharma S. Physiology, Thyroid Hormone. [Updated 2021 May 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK500006/
Safety review of liothyronine use: a 20 year observational follow up study
https://www.endocrine-abstracts.org/ea/0038/ea0038OC5.6
Effects of Long-Term Combination LT4 and LT3 Therapy for Improving Hypothyroidism and Overall Quality of Life
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5965938/
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021402s024s028lbl.pdf
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021402s024s028lbl.pdf
https://www.rxlist.com/cytomel-drug.htm#medguide
https://s3-us-west-2.amazonaws.com/drugbank/fda_labels/DB00279.pdf?1551815137
Thyroid Cancer Advocates 